Methods and apparatus for localized administration of inhibitory moieties to a patient

Abstract

Methods and devices are provided for the localized administration to a patient of moieties effective for inhibiting unwanted cellular growth, including restenosis of an artery treated with a stent implant for blockage of blood flow by an atherosclerotic lesion. After implantation of a medical device capable of moiety-binding, moieties effective at inhibiting unwanted cellular growth are administered locally to a patient. In this manner the deleterious side-effects of systemic administration of moieties are avoided. Upon localized administration, the moieties bind the medical device, rendering the medical device itself capable of inhibiting unwanted cellular growth. According to an embodiment, after implantation of a stent, radioactive moieties specific for receptors immobilized on the stent surface are locally administered using a balloon perfusion catheter. The moieties bind specifically the receptors, becoming immobilized thereto, thereby rendering the stent radioactive and effective for inhibiting restenosis.

1 . A method of reducing restenosis in a patient vessel, comprising:
 implanting a stent in the vessel, wherein the stent includes   a surface and a first member of a specific binding pair disposed on the surface   deploying a perfusion catheter in the vessel in a vicinity of the stent;   inflating an upstream balloon portion and a downstream balloon portion of the perfusion catheter to block vessel flow upstream and downstream of the stent; and   delivering a binding solution to the stent via the perfusion catheter, wherein the binding solution includes a restenosis-inhibiting moiety comprising a second member of the specific binding pair.   
     
     
         2 . The method of  claim 1 , wherein the restenosis-inhibitory moiety comprises a radioactive moiety. 
     
     
         3 . The method of  claim 1 , wherein the restenosis-inhibitory moiety comprises a neutron-capture moiety; and
 the method further comprising exposing the stent to a neutron flux.   
     
     
         4 . The method of  claim 1  wherein the first and second members of the specific binding pair comprise first and second biomolecules being compatible to form a binding interaction with one another. 
     
     
         5 . (canceled) 
     
     
         6 . The method of  claim 1  wherein the first member is immobilized directly to the stent. 
     
     
         7 . The method of  claim 1  wherein the first member is immobilized to a coating disposed on the stent. 
     
     
         8 . (canceled) 
     
     
         9 . (canceled) 
     
     
         10 . The method of  claim 1  further comprising repeating, at least one time, the step of delivering a binding solution to the stent via the perfusion catheter. 
     
     
         11 . (canceled) 
     
     
         12 . (canceled) 
     
     
         13 . The method of  claim 3  further comprising repeating, at least one time, the step of exposing the stent to a neutron flux. 
     
     
         14 - 20 . (canceled) 
     
     
         21 . The method of  claim 1 , further comprising delivering a wash solution to purge the region upstream and downstream of the stent prior to delivering the binding solution. 
     
     
         22 . The method of  claim 21 , further comprising
 delivering a second wash solution to purge the binding solution from the region upstream and downstream of the stent; and   withdrawing the perfusion catheter from the vessel.   
     
     
         23 . A method of reducing restenosis in a patient vessel, comprising:
 implanting a stent in the vessel, wherein the stent includes a surface and a first member of a specific binding pair disposed on the surface;   deploying a perfusion catheter in the vessel in a vicinity of the stent;   inflating an upstream balloon portion and a downstream balloon portion of the perfusion catheter to block vessel flow upstream and downstream of the stent;   delivering a wash solution to purge the vicinity of the stent; and   delivering a binding solution to the stent via the perfusion catheter, wherein the binding solution includes a restenosis-inhibiting moiety coupled to a second member of the specific binding pair.   
     
     
         24 . The method of  claim 23 , further comprising delivering a second wash solution to purge the binding solution from the region upstream and downstream of the stent. 
     
     
         25 . The method of  claim 24 , further comprising leaving the binding solution in contact with the stent for a period of time ranging from 1 second to 30minutes before delivering the second wash. 
     
     
         26 . The method of  claim 23 , wherein the wash solution comprises an ionic buffered saline. 
     
     
         27 . The method of  claim 23 , wherein the wash solution has at least one characteristic similar to blood. 
     
     
         28 . The method of  claim 23 , wherein the restenosis-inhibitory moiety comprises at least one of a radioactive moiety or a neutron-capture moiety. 
     
     
         29 . The method of  claim 23 , wherein the first and second members of the specific binding pair comprise compatible biomolecules. 
     
     
         30 . The method of  claim 23 , wherein the stent includes a plurality of different first members of the specific binding pair and the binding solution includes a plurality of different second members of the specific binding pair, wherein each of the different second members of the specific binding pair is configured to bind with a selected first member of the specific binding pair and there is substantially no cross-reactivity between the different first members of the specific binding pair and the different second members of the specific binding pair. 
     
     
         31 . A method of reducing restenosis in a patient vessel, comprising:
 deploying in the vessel a catheter that includes a first balloon having a stent positioned thereon, and second and third balloons proximal and distal to the first balloon, wherein the stent includes a surface and a first member of a specific binding pair disposed on the surface;   deploying the stent by inflating the first balloon;   inflating the second and third balloons to block vessel flow upstream and downstream of the stent; and   delivering a binding solution to the stent via the catheter, wherein the binding solution includes a restenosis-inhibiting moiety coupled to a second member of the specific binding pair.   
     
     
         32 . The method of  claim 31 , further comprising delivering a first wash solution via the catheter after inflating the second and third balloons to purge the region upstream and downstream of the stent. 
     
     
         33 . The method of  claim 32 , further comprising delivering a second wash solution via the catheter after delivering the binding solution to the stent. 
     
     
         34 . The method of  claim 33 , further comprising continuing to deliver the second wash solution until substantially no restenosis-inhibiting moiety is detectable in the wash solution. 
     
     
         35 . The method of  claim 31 , wherein the binding solution is delivered to the stent via inlet and outlet ports in the catheter. 
     
     
         36 . The method of  claim 31 , wherein the binding solution is delivered to the stent via the first balloon. 
     
     
         37 . The method of  claim 36 , wherein the second balloon is permeable to the second member of the binding pair.